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Thrombocytopenia 7(THC7)

MedGen UID:
1768257
Concept ID:
C5436874
Disease or Syndrome
Synonym: THROMBOCYTOPENIA, AUTOSOMAL DOMINANT, 7
 
Gene (location): IKZF5 (10q26.13)
 
Monarch Initiative: MONDO:0030867
OMIM®: 619130

Definition

Thrombocytopenia-7 (THC7) is an autosomal dominant disorder characterized by reduced peripheral platelet count. The expression and severity of the disorder is highly variable: some patients have no bleeding symptoms, whereas other have recurrent petechiae, epistaxis, or more severe bleeding episodes. A common finding is decreased alpha-granules in the platelets. There are variable findings on light and electron microscopic analysis: some patients have normal platelet morphology, whereas others show abnormal platelet morphology with cytoskeletal defects. Flow cytometric studies may show reduced expression of platelet membrane glycoproteins and activation markers (summary by Lentaigne et al., 2019 and Leinoe et al., 2021). For a general phenotypic description and a discussion of genetic heterogeneity of thrombocytopenia, see 313900. [from OMIM]

Clinical features

From HPO
Post-partum hemorrhage
MedGen UID:
18592
Concept ID:
C0032797
Pathologic Function
Significant maternal hemorrhage/blood loss following deilvery of a child.
Thrombocytopenia
MedGen UID:
52737
Concept ID:
C0040034
Disease or Syndrome
A reduction in the number of circulating thrombocytes.
Impaired ristocetin-induced platelet aggregation
MedGen UID:
868749
Concept ID:
C4023154
Pathologic Function
Abnormal response to ristocetin as manifested by reduced or lacking aggregation of platelets upon addition of ristocetin.
Impaired arachidonic acid-induced platelet aggregation
MedGen UID:
868750
Concept ID:
C4023155
Pathologic Function
Abnormal response to arachidonic acid as manifested by reduced or lacking aggregation of platelets upon addition of arachidonic acid.
Impaired collagen-induced platelet aggregation
MedGen UID:
870264
Concept ID:
C4024703
Finding
Abnormal response to collagen or collagen-mimetics as manifested by reduced or lacking aggregation of platelets upon addition collagen or collagen-mimetics.
Impaired ADP-induced platelet aggregation
MedGen UID:
870824
Concept ID:
C4025282
Finding
Abnormal platelet response to ADP as manifested by reduced or lacking aggregation of platelets upon addition of ADP.
Reduced platelet dense granules
MedGen UID:
1785275
Concept ID:
C5539663
Finding
Decreased number of platelet dense granules, a type of platelet organelle.
Reduced platelet alpha granules
MedGen UID:
1789060
Concept ID:
C5539664
Finding
A reduced number of platelet alpha granules.

Professional guidelines

PubMed

Even-Or E, Schiesel G, Simanovsky N, NaserEddin A, Zaidman I, Elpeleg O, Mor-Shaked H, Stepensky P
Bone 2022 Jan;154:116229. Epub 2021 Oct 8 doi: 10.1016/j.bone.2021.116229. PMID: 34624559
Somasegar S, Hoppenot C, Kuchta K, Sereika A, Khandekar J, Rodriguez G, Moore E, Hurteau J, Vogel TJ
Gynecol Oncol 2021 Nov;163(2):220-228. Epub 2021 Sep 9 doi: 10.1016/j.ygyno.2021.08.027. PMID: 34511240
Sharif S, Zahid I, Routledge T, Scarci M
Interact Cardiovasc Thorac Surg 2011 Jun;12(6):1040-5. Epub 2011 Mar 8 doi: 10.1510/icvts.2010.256289. PMID: 21388982

Recent clinical studies

Etiology

Touzeau C, Perrot A, Hulin C, Manier S, Macro M, Chretien ML, Karlin L, Escoffre M, Jacquet C, Tiab M, Leleu X, Avet-Loiseau H, Jobert A, Planche L, Corre J, Moreau P
Blood 2024 May 16;143(20):2029-2036. doi: 10.1182/blood.2023023597. PMID: 38394666
Vergote I, Pérez-Fidalgo JA, Hamilton EP, Valabrega G, Van Gorp T, Sehouli J, Cibula D, Levy T, Welch S, Richardson DL, Guerra EM, Scambia G, Henry S, Wimberger P, Miller DS, Klat J, Martínez-Garcia J, Raspagliesi F, Pothuri B, Romero I, Bergamini A, Slomovitz B, Schochter F, Høgdall E, Fariñas-Madrid L, Monk BJ, Michel D, Kauffman MG, Shacham S, Mirza MR, Makker V; ENGOT-EN5/GOG-3055/SIENDO Investigators
J Clin Oncol 2023 Dec 10;41(35):5400-5410. Epub 2023 Sep 5 doi: 10.1200/JCO.22.02906. PMID: 37669480
O'Connor OA, Horwitz S, Masszi T, Van Hoof A, Brown P, Doorduijn J, Hess G, Jurczak W, Knoblauch P, Chawla S, Bhat G, Choi MR, Walewski J, Savage K, Foss F, Allen LF, Shustov A
J Clin Oncol 2015 Aug 10;33(23):2492-9. Epub 2015 Jun 22 doi: 10.1200/JCO.2014.59.2782. PMID: 26101246Free PMC Article
O'Brien ME, Ciuleanu TE, Tsekov H, Shparyk Y, Cuceviá B, Juhasz G, Thatcher N, Ross GA, Dane GC, Crofts T
J Clin Oncol 2006 Dec 1;24(34):5441-7. doi: 10.1200/JCO.2006.06.5821. PMID: 17135646
Jain R, Chartash E, Susin M, Furie R
Semin Arthritis Rheum 1994 Dec;24(3):173-82. doi: 10.1016/0049-0172(94)90073-6. PMID: 7899875

Diagnosis

Touzeau C, Perrot A, Hulin C, Manier S, Macro M, Chretien ML, Karlin L, Escoffre M, Jacquet C, Tiab M, Leleu X, Avet-Loiseau H, Jobert A, Planche L, Corre J, Moreau P
Blood 2024 May 16;143(20):2029-2036. doi: 10.1182/blood.2023023597. PMID: 38394666
Zhang Y, Suo SS, Yang HJ, Zhou XP, You LS, Yu WJ, Wang ZM, Jin J
J Cancer Res Clin Oncol 2020 Feb;146(2):357-365. Epub 2020 Jan 14 doi: 10.1007/s00432-019-03120-w. PMID: 31938902Free PMC Article
Paludo J, Abeykoon JP, Kumar S, Shreders A, Ailawadhi S, Gertz MA, Kourelis T, King RL, Reeder CB, Leung N, Kyle RA, Buadi FK, Habermann TM, Dingli D, Witzig TE, Dispenzieri A, Lacy MQ, Go RS, Lin Y, Gonsalves WI, Warsame R, Lust JA, Rajkumar SV, Ansell SM, Kapoor P
Br J Haematol 2017 Oct;179(1):98-105. Epub 2017 Aug 8 doi: 10.1111/bjh.14826. PMID: 28786474
Bryant N, Watts R
Clin Pediatr (Phila) 2011 Mar;50(3):225-30. Epub 2010 Nov 22 doi: 10.1177/0009922810385676. PMID: 21098529
Jain R, Chartash E, Susin M, Furie R
Semin Arthritis Rheum 1994 Dec;24(3):173-82. doi: 10.1016/0049-0172(94)90073-6. PMID: 7899875

Therapy

Touzeau C, Perrot A, Hulin C, Manier S, Macro M, Chretien ML, Karlin L, Escoffre M, Jacquet C, Tiab M, Leleu X, Avet-Loiseau H, Jobert A, Planche L, Corre J, Moreau P
Blood 2024 May 16;143(20):2029-2036. doi: 10.1182/blood.2023023597. PMID: 38394666
Vergote I, Pérez-Fidalgo JA, Hamilton EP, Valabrega G, Van Gorp T, Sehouli J, Cibula D, Levy T, Welch S, Richardson DL, Guerra EM, Scambia G, Henry S, Wimberger P, Miller DS, Klat J, Martínez-Garcia J, Raspagliesi F, Pothuri B, Romero I, Bergamini A, Slomovitz B, Schochter F, Høgdall E, Fariñas-Madrid L, Monk BJ, Michel D, Kauffman MG, Shacham S, Mirza MR, Makker V; ENGOT-EN5/GOG-3055/SIENDO Investigators
J Clin Oncol 2023 Dec 10;41(35):5400-5410. Epub 2023 Sep 5 doi: 10.1200/JCO.22.02906. PMID: 37669480
Twu CW, Lin PJ, Tsou HH, Liu YC, Jiang RS, Liang KL, Lin TY, Wang WY, Lin JC
Head Neck 2022 Jun;44(6):1453-1461. Epub 2022 Apr 1 doi: 10.1002/hed.27044. PMID: 35362634
O'Connor OA, Horwitz S, Masszi T, Van Hoof A, Brown P, Doorduijn J, Hess G, Jurczak W, Knoblauch P, Chawla S, Bhat G, Choi MR, Walewski J, Savage K, Foss F, Allen LF, Shustov A
J Clin Oncol 2015 Aug 10;33(23):2492-9. Epub 2015 Jun 22 doi: 10.1200/JCO.2014.59.2782. PMID: 26101246Free PMC Article
O'Brien ME, Ciuleanu TE, Tsekov H, Shparyk Y, Cuceviá B, Juhasz G, Thatcher N, Ross GA, Dane GC, Crofts T
J Clin Oncol 2006 Dec 1;24(34):5441-7. doi: 10.1200/JCO.2006.06.5821. PMID: 17135646

Prognosis

Park JW, Kim YJ, Kim DY, Bae SH, Paik SW, Lee YJ, Kim HY, Lee HC, Han SY, Cheong JY, Kwon OS, Yeon JE, Kim BH, Hwang J
J Hepatol 2019 Apr;70(4):684-691. Epub 2018 Dec 6 doi: 10.1016/j.jhep.2018.11.029. PMID: 30529387
Stein EM, DiNardo CD, Fathi AT, Pollyea DA, Stone RM, Altman JK, Roboz GJ, Patel MR, Collins R, Flinn IW, Sekeres MA, Stein AS, Kantarjian HM, Levine RL, Vyas P, MacBeth KJ, Tosolini A, VanOostendorp J, Xu Q, Gupta I, Lila T, Risueno A, Yen KE, Wu B, Attar EC, Tallman MS, de Botton S
Blood 2019 Feb 14;133(7):676-687. Epub 2018 Dec 3 doi: 10.1182/blood-2018-08-869008. PMID: 30510081Free PMC Article
O'Connor OA, Horwitz S, Masszi T, Van Hoof A, Brown P, Doorduijn J, Hess G, Jurczak W, Knoblauch P, Chawla S, Bhat G, Choi MR, Walewski J, Savage K, Foss F, Allen LF, Shustov A
J Clin Oncol 2015 Aug 10;33(23):2492-9. Epub 2015 Jun 22 doi: 10.1200/JCO.2014.59.2782. PMID: 26101246Free PMC Article
Sharif S, Zahid I, Routledge T, Scarci M
Interact Cardiovasc Thorac Surg 2011 Jun;12(6):1040-5. Epub 2011 Mar 8 doi: 10.1510/icvts.2010.256289. PMID: 21388982
O'Brien ME, Ciuleanu TE, Tsekov H, Shparyk Y, Cuceviá B, Juhasz G, Thatcher N, Ross GA, Dane GC, Crofts T
J Clin Oncol 2006 Dec 1;24(34):5441-7. doi: 10.1200/JCO.2006.06.5821. PMID: 17135646

Clinical prediction guides

Twu CW, Lin PJ, Tsou HH, Liu YC, Jiang RS, Liang KL, Lin TY, Wang WY, Lin JC
Head Neck 2022 Jun;44(6):1453-1461. Epub 2022 Apr 1 doi: 10.1002/hed.27044. PMID: 35362634
Somashekhar SP, Prasanna G, Jaka R, Rauthan A, Murthy HS, Karanth S
Natl Med J India 2016 Sep-Oct;29(5):262-266. PMID: 28098079
Panzuto F, Rinzivillo M, Fazio N, de Braud F, Luppi G, Zatelli MC, Lugli F, Tomassetti P, Riccardi F, Nuzzo C, Brizzi MP, Faggiano A, Zaniboni A, Nobili E, Pastorelli D, Cascinu S, Merlano M, Chiara S, Antonuzzo L, Funaioli C, Spada F, Pusceddu S, Fontana A, Ambrosio MR, Cassano A, Campana D, Cartenì G, Appetecchia M, Berruti A, Colao A, Falconi M, Delle Fave G
Oncologist 2014 Sep;19(9):966-74. Epub 2014 Aug 12 doi: 10.1634/theoncologist.2014-0037. PMID: 25117065Free PMC Article
Sharif S, Zahid I, Routledge T, Scarci M
Interact Cardiovasc Thorac Surg 2011 Jun;12(6):1040-5. Epub 2011 Mar 8 doi: 10.1510/icvts.2010.256289. PMID: 21388982
Steinberg M
Clin Ther 2008 Sep;30(9):1590-617. doi: 10.1016/j.clinthera.2008.09.015. PMID: 18840366

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